The ultimate goal of this proposal is to test the following hypotheses: a) hypercarbic respiratory failure during weaning from mechanical ventilation usually results from diaphragm fatigue, and b) diaphragm fatigue results from an imbalance between the mechanical load on the respiratory muscles and their endurance. Three studies are presented. The aim of Protocol 1 is to verify the importance of diaphragm fatigue in the pathophysiology of hypercarbic respirtory failure in patients. The response of the diaphragm to bilateral phrenic stimulations will be evaluated in ventilator-dependent patients before and after failed weaning attempts. Diaphragm fatigue will be defined as a fall in the transdiaphragmatic twitch pressure between pre and postweaning states. The results will determine: a) the incidence of fatigue, and b) whether fatigue is a failure in neuromuscular transmission and/or excitation contraction coupling. This study will also give information concerning: a) the time necessary for recovery from fatigue, and b) the predictive value of less invasive measurements such as inspiratory work, inspiratory muscle strength, airway occlusion pressure, transdiaphragmatic pressure (PDI), breathing pattern, thoracoabdominal motion, the power spectral analysis of the diaphragm EMG, and gas exchange variables. The aim of Protocol 2 is to validate PDI generated by bilateral phrenic stimulation as an index of diaphragm contractility in normal man. In normal volunteers, PDI produced by bilateral phrenic nerve stimulation will be evaluated as a function of lung volume during relaxation and while thoracoabdominal shape is being systematically altered by a pneumatic device which displaces the thorax and abdomen along an isovolume line. It will thus be determined whether abdominal volume at a constant lung volume has a significant independent effect on diaphragm function. The specific aim of Protocol 3 is to determine the relationship between PDI generated by bilateral phrenic stimulation and regional diaphragm mechanics in the dog. To assess the limitations of PDI as an index of global diaphragm function, regional diaphragm function and its relationship to PDI will be evaluated in the dog. By adapting the videoroentgenographic marker technique for studying regional lung function to the diaphragm, the regional contractility will be evaluated in vivo under conditions of defined initial lengths and loads.